There is need for nutrition-derived disease prevention and disease treatment support which would intelligently and predictably modify host response against inappropriate or inadequate reaction of the body to an existing or a potential disease. This is a novel category in disease prevention and treatment. This category is different from the concept of enhancing prevention or treatment focused on modification of the prevention/intervention modalities, e.g. modification of vaccine or a drug. This approach is also different from disease prevention based on, e.g. good nutrition or physical exercise which provides general support to the organism. The proposed novel category would include compounds to intelligently repair host mechanisms that may trigger disease or aggravate the existing disease. Inotilone, a natural compound derived from Inonotus sp edible fungi, exemplifies the new prevention/treatment category described here as coherent biological response modifier (cBMR).
Inotilone, 5-methyl-3(2H)-furanone derivative, and related phenylpropanoid polyketides from Inonotus sp. have been previously shown to be potent anti-inflammatory agents and inhibitors of cyclooxygenase and xanthone oxidase enzymes (Wangun H V, et al. Org Biomol Chem. 2006 Jul. 7; 4(13):2545-8); modulate immunological and inflammatory responses (Pan, M H et al, J. Agric. Food Chem 2009, 57(11):4467-4477; Lull, C et al. Mediators. Inflamm. 2005, 2005(2): 63-80); show antihyperglycemic and antilipidperoxidative effects (Sun, J E et al., J. Ethnopharmacology, 118(1):7-13, 2008); and antitumor effects (Youn, M J et al., World J Gastroenterol. 14(4): 511-517, 2008; Kahlos, K et al. Planta Medica, 52(6):554).
Inotilone blocked protein and mRNA expression of iNOS but not COX-2. Instead, inotilone inhibited prostaglandin E(2) production through decreasing the enzyme activity of COX-2. The repression of iNOS but not COX-2 expression may come from the differential effect of inotilone on nuclear factor-kappaB (NFkappaB) and CCAAT/enhancer-binding protein beta Treatment with inotilone resulted in the reduction of LPS-induced nuclear translocation of NFkappaB subunit and the NFkappaB-dependent transcriptional activity by blocking phosphorylation of inhibitor kappaB (IkappaB) alpha and p65 and subsequent degradation of inhibitor kappaBalpha. Inotilone also inhibited LPS-induced activation of PI3K/Akt and extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase. (Kuo, Y C et al, Mol Nutr Food Res. 53(11):1386-95, 2009).